4.5 Review

Advances in the discovery of heterocyclic-based drugs against Alzheimer's disease

Related references

Note: Only part of the references are listed.
Review Biochemistry & Molecular Biology

Tacrine-Based Hybrids: Past, Present, and Future

Anna Bubley et al.

Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by Aβ aggregation, tau hyperphosphorylation, and loss of cholinergic neurons. AD is also associated with oxidative stress, metal dyshomeostasis, inflammation, and cell cycle dysregulation. In this review, THA-based hybrids are summarized as potential anti-AD agents, highlighting strategies for drug design that have led to cognitive improvements and reduced hepatotoxicity.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Biochemistry & Molecular Biology

Chromone-based monoamine oxidase B inhibitor with potential iron-chelating activity for the treatment of Alzheimer's disease

Changjun Zhang et al.

Summary: Based on the multitarget-directed ligands (MTDLs) strategy, a series of chromone-hydroxypyridinone hybrids were designed, synthesised, and evaluated as potential multimodal anti-AD ligands. Compound 17d showed favorable iron-chelating potential and selective hMAO-B inhibitory activity, and was able to cross the blood-brain barrier and ameliorate cognitive impairment in AD mice. Despite its undesired pharmacokinetic property, 17d remains a promising multifaceted agent worth further investigation.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2023)

Review Chemistry, Medicinal

Recent Developments in Tacrine-based Hybrids as a Therapeutic Option for Alzheimer's Disease

Cem Yamali et al.

Summary: Alzheimer's disease is an irreversible neurodegenerative disorder among the elderly, and current drugs cannot delay its progression. This article discusses the need for novel anti-Alzheimer's drugs that target multiple pathways in the disease, rather than the traditional one drug-one target concept. The study focuses on modifications made to tacrine to develop promising anti-AD drug candidates.

MINI-REVIEWS IN MEDICINAL CHEMISTRY (2023)

Article Clinical Neurology

The effect of the calcium channel blocker nimodipine on hippocampal BDNF/Ach levels in rats with experimental cognitive impairment

Atilla Topcu et al.

Summary: Alzheimer's disease occurs in 10% to 30% of individuals aged 65 or older worldwide. Nimodipine appears to have the potential to reverse cognitive impairment-induced dysfunction through its regulatory effect on BDNF, Ach, and AChE pathways in the hippocampus and prefrontal cortex.

NEUROLOGICAL RESEARCH (2023)

Review Neurosciences

Challenges and Opportunities of Metal Chelation Therapy in Trace Metals Overload-Induced Alzheimer's Disease

Vinay Chaudhari et al.

Summary: Essential trace metals like zinc (Zn), iron (Fe), and copper (Cu) are crucial for the healthy functioning of body organs, including the brain. However, abnormal accumulation of trace metals in the brain has been linked to neuronal degeneration and neurodegeneration in Alzheimer's disease (AD). The therapeutic potential of metal chelation in treating AD is still uncertain, despite its hypothesized benefits. This review evaluates the impact of trace metals on brain functioning and their association with neurodegeneration in AD, and explores the potential of metal chelators as a management option for AD patients.

NEUROTOXICITY RESEARCH (2023)

Review Chemistry, Multidisciplinary

SAR studies of quinoline and derivatives as potential treatments for Alzheimer's disease

Zhao-Hui Li et al.

Summary: Quinoline analogs, widely used in medicinal chemistry and organic synthesis, have attracted extensive attention due to their diverse biological activities, including anti-Alzheimer's disease activity. This review summarizes recent research on quinoline and related analogs as anti-Alzheimer's disease agents from 2001 to 2022, focusing on structure-activity relationships and molecular binding modes. The findings provide valuable insights for the rational design of more effective and target-specific drugs for Alzheimer's disease.

ARABIAN JOURNAL OF CHEMISTRY (2023)

Review Biochemistry & Molecular Biology

Modulation of L-type calcium channels in Alzheimer?s disease: A potential therapeutic target

Chelsea A. Crossley et al.

Summary: Calcium is essential for various signaling pathways and cellular processes in the human body. L-type calcium channels (LTCCs) play a critical role in the nervous system, mediating neurotransmitter release, synaptic integration, and plasticity. Dysfunction of LTCCs has been linked to aging and Alzheimer's Disease (AD), making them a potential target for AD treatment. However, the mechanisms by which LTCCs contribute to AD are still unclear. This review provides an overview of the structure, function, and modulation of LTCCs, suggesting that targeting molecular pathways that up-regulate LTCCs may be a more promising approach in AD.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2023)

Review Pharmacology & Pharmacy

Physiologic Functions and Therapeutic Applications of α7 Nicotinic Acetylcholine Receptor in Brain Disorders

Chien-Hsing Lee et al.

Summary: Accumulating data suggests that alpha 7 nicotinic acetylcholine receptors (alpha 7nAChRs) are important therapeutic targets for Alzheimer's disease (AD) and schizophrenia. Alpha 7nAChRs are widely distributed in the brain and play significant roles in neurotransmitter release and cognitive functioning. Studies have shown that genetic variations affecting CHRNA7 expression or causing alpha 7nAChR dysfunction are associated with various brain disorders. This review summarizes the current findings and characteristics of alpha 7nAChRs in common brain diseases, providing insights for innovative research and treatments targeting alpha 7nAChRs.

PHARMACEUTICS (2023)

Review Chemistry, Medicinal

Development of new Alzheimer's disease drug candidates using donepezil as a key model

Kholoud Eissa et al.

Summary: Alzheimer's disease is a common geriatric disease characterized by complex pathology. Donepezil, a potent approved drug for AD, has effects on multiple AD-related processes. By hybridizing DNP with other drugs targeting AD, multi-target drugs can be designed for AD treatment.

ARCHIV DER PHARMAZIE (2023)

Article Biochemistry & Molecular Biology

Chemical library design, QSAR modeling and molecular dynamics simulations of naturally occurring coumarins as dual inhibitors of MAO-B and AChE

Yassir Boulaamane et al.

Summary: Coumarins are important in medicinal chemistry and have various pharmacological properties. Through virtual screening, ten coumarin derivatives with dual-target inhibitory activity were identified.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS (2023)

Article Biochemistry & Molecular Biology

Novel benzothiazole derivatives as multitargeted-directed ligands for the treatment of Alzheimer's disease

Donia E. Hafez et al.

Summary: Introduced a multi-targeted ligand for neurodegenerative diseases, such as Alzheimer's disease, which offers an improved therapeutic alternative compared to the traditional one-target, one-molecule approach. Certain compounds showed potential for multi-targeting by evaluating their interactions with AChE, BuChE, and MAO-B, suggesting their potential as lead structures for developing new multi-targeting anti-AD agents.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2023)

Review Neurosciences

Amyloid-beta aggregation implicates multiple pathways in Alzheimer's disease: Understanding the mechanisms

Musa O. Iliyasu et al.

Summary: Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by tau pathology and accumulation of amyloid-beta (Aβ). Aβ aggregation leads to oxidative stress, inflammatory cascade, and caspase activation, causing hyperphosphorylation of tau protein and formation of neurofibrillary tangles (NFTs). Acetylcholine degradation is accelerated, resulting in neurotransmitter deficiency and cognitive impairment. AD research is necessary to identify novel compounds for treatment and prevention, including those targeting Aβ, tau, neurotransmitter modulation, neuroinflammation, neuroprotection, and cognition enhancement.

FRONTIERS IN NEUROSCIENCE (2023)

Review Chemistry, Multidisciplinary

Enhancing the Therapeutic Effect in Alzheimer's Disease Drugs: The role of Polypharmacology and Cholinesterase inhibitors

M. Margarida Martins et al.

Summary: Alzheimer's disease (AD) is a devastating syndrome that accounts for a significant portion of dementia cases worldwide. Traditional approaches to drug design for AD have become obsolete due to the complex pathological mechanisms involved, leading to the emergence of polypharmacology. Multi-target directed ligands (MTDLs), particularly those targeting cholinesterases, are gaining attention as potential therapies that can regulate multiple targets in the disease network. This review discusses the current hypotheses and therapeutic targets for AD, the concept of polypharmacology, and the importance of cholinesterases in the pathogenesis and biochemical processes of AD, with a focus on the development of cholinesterase-based MTDLs.

CHEMISTRYSELECT (2023)

Article Oncology

Immune and pathologic responses in patients with localized prostate cancer who received daratumumab (anti-CD38) or edicotinib (CSF-1R inhibitor)

Bilal A. Siddiqui et al.

Summary: This study aimed to explore the safety and efficacy of Daratumumab and edicotinib in the treatment of localized prostate cancer. The results showed that these two drugs were safe to use and did not induce complete remission. However, Daratumumab treatment led to a decreased frequency of CD38(+) immune cells in prostate tumors, bone marrow, and peripheral blood mononuclear cells (PBMCs), while edicotinib did not consistently affect CSF-1R(+) immune cells.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2023)

Review Biochemistry & Molecular Biology

Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders

Ramakrishna Nirogi et al.

Summary: Serotonin-6 (5-HT6) receptor, a G-protein-coupled receptor, plays a key role in the regulation of various functions in the nervous system. Clinical studies have shown that 5-HT6 receptor antagonists have potential in treating cognitive deficits associated with Alzheimer's disease (AD) and neuropsychiatric symptoms in dementia. However, the outcomes of phase 3 trials for these antagonists have been disappointing. Masupirdine, a selective 5-HT6 receptor antagonist, has shown promise in reducing agitation/aggression-like behaviors in animal models and may have potential benefits for agitation and psychosis in AD, but further trials are needed.

BIOMOLECULES (2023)

Review Biochemistry & Molecular Biology

Role of calcium dysregulation in Alzheimer's disease and its therapeutic implications

Maithili Joshi et al.

Summary: Calcium dysregulation is associated with Alzheimer's disease (AD) and understanding its mechanisms is crucial for developing new therapies. This review provides a detailed account of the physiology of calcium homeostasis and its dysregulation in AD, as well as discussions on calcium channel blockers and multitarget molecules explored in AD research.

CHEMICAL BIOLOGY & DRUG DESIGN (2023)

Review Clinical Neurology

Histaminergic neurotransmission in aging and Alzheimer's disease: A review of therapeutic opportunities and gaps

Abhijit Satpati et al.

Summary: Alzheimer's disease (AD) is characterized by the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain. Sleep dysfunction, including sleep fragmentation and excessive daytime sleepiness, is a common symptom in AD. Histaminergic neurons in the tuberomammillary nucleus play a role in cognition and arousal, and targeting histaminergic receptors has shown therapeutic potential in AD models.

ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS (2023)

Review Biochemistry & Molecular Biology

Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer's Disease

Rudolf Vrabec et al.

Summary: Alzheimer's disease is a common cause of dementia in the elderly population, but there is no effective treatment currently available. The increasing life expectancy worldwide is expected to lead to a significant rise in Alzheimer's disease rates, necessitating the urgent search for new drugs. Alkaloids, particularly harmine and isoquinoline alkaloids, show promise as multi-target compounds for Alzheimer's disease by inhibiting key enzymes involved in its pathophysiology. However, further research is needed to explore their mechanisms of action and develop potentially better synthetic analogues.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Biochemistry & Molecular Biology

Immunomodifying and neuroprotective effects of noscapine: Implications for multiple sclerosis, neurodegenerative, and psychiatric disorders

Meric A. Altinoz et al.

Summary: Noscapine is a versatile alkaloid with various pharmacological effects that can be used to treat neurodegenerative and psychiatric diseases such as multiple sclerosis, Parkinson's Disease, Amyotrophic Lateral Sclerosis, stroke, anxiety, depression, and Alzheimer's Disease.

CHEMICO-BIOLOGICAL INTERACTIONS (2022)

Review Chemistry, Medicinal

Current trends of benzothiazoles in drug discovery: a patent review (2015-2020)

Christine Shing Wei Law et al.

Summary: Benzothiazole is a bicyclic ring system composed of thiazole and benzene rings, and it serves as an important pharmacophore in many marketed drugs. This review summarizes 55 benzothiazole-related patents filed from 2015 to 2020, covering a wide range of pharmacological activities. The patents were categorized and discussed based on their respective group of target diseases, including metabolic diseases, cancer, inflammation, neurodegeneration, viral diseases, bacterial infections, fibrosis, and thrombosis.

EXPERT OPINION ON THERAPEUTIC PATENTS (2022)

Article Neurosciences

Recent Advances in Molecular Pathways and Therapeutic Implications Targeting Mitochondrial Dysfunction for Alzheimer's Disease

Rishika Dhapola et al.

Summary: Alzheimer's disease is a neurodegenerative disorder caused by mitochondrial dysfunction, with drugs targeting mitochondria in clinical trials. Modulation of mitochondrial dynamics and reduction of ROS production are potential therapeutic strategies.

MOLECULAR NEUROBIOLOGY (2022)

Article Biochemistry & Molecular Biology

Synthesis, structural elucidation, DNA binding, cleavage, AChE and BuChE cholinesterase efficiencies of metal complexes with 1,10-phenanthroline scaffold

E. H. Edinsha Gladis et al.

Summary: A series of metal complexes containing a 1,10-phenanthroline scaffold were designed and synthesized, showing effective antibacterial and DNA cleavage capabilities. The synthesized 1,10-phenanthroline derivative demonstrated strong inhibitory effects on cholinesterase enzymes and high binding affinity to DNA.

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS (2022)

Review Geriatrics & Gerontology

Multi-Targets: An Unconventional Drug Development Strategy for Alzheimer's Disease

Cheng-Xin Gong et al.

Summary: Alzheimer's disease is a progressive neurodegenerative disorder that currently lacks effective treatments to slow or halt its progression. Recent changes in drug development strategy include shifting to targets other than amyloid and improving clinical trial designs. There is a growing recognition of the need for a paradigm shift towards multi-target approaches in AD drug development.

FRONTIERS IN AGING NEUROSCIENCE (2022)

Review Biochemistry & Molecular Biology

Inhibition of colony stimulating factor-1 receptor (CSF-1R) as a potential therapeutic strategy for neurodegenerative diseases: opportunities and challenges

Jinming Han et al.

Summary: This review article summarizes the recent advances in the use of CSF-1R inhibitors for treating neurodegenerative diseases and discusses potential challenges for clinical application.

CELLULAR AND MOLECULAR LIFE SCIENCES (2022)

Article Chemistry, Applied

Benzothiazole based fluorescent probes for the detection of biomolecules, physiological conditions, and ions responsible for diseases

Samarpita Das et al.

Summary: Benzothiazole-based fluorescent probes, decorated with chemical fragments capable of detecting specific analytes, selectively interact with various analytes and change their luminescence features for detection. These probes have advantages of large Stokes shift, high quantum yields, and excellent color transitions, and can be applied for disease diagnosis.

DYES AND PIGMENTS (2022)

Article Biochemistry & Molecular Biology

Brain-penetrant calcium channel blockers are associated with a reduced incidence of neuropsychiatric disorders

Lucy Colbourne et al.

Summary: Calcium channel blockers (CCBs) vary in their ability to penetrate the brain. Research has shown that CCBs that easily penetrate the brain are associated with lower incidence of neuropsychiatric disorders. These findings are significant for the repurposing and development of CCBs with enhanced and more selective central actions for the treatment of psychiatric and neurodegenerative disorders.

MOLECULAR PSYCHIATRY (2022)

Review Pharmacology & Pharmacy

Pivotal role of nitrogen heterocycles in Alzheimer's disease drug discovery

Shikha Kumari et al.

Summary: Alzheimer's disease is a progressive neurodegenerative disease with limited clinical options. Research is ongoing to find effective anti-AD compounds, and this review explores previous strategies, research findings, and success stories. Strategies for designing and developing small molecules for AD treatment are also proposed.

DRUG DISCOVERY TODAY (2022)

Article Chemistry, Physical

In vitro studies of a series of synthetic compounds for their anti-acetylcholinesterase activities identified arylpyrano[2,3-f]coumarins as hit compounds

Erlon Ferreira Martin et al.

Summary: Alzheimer's disease is a prevalent neurodegenerative disease, and a compound family called pyranochromenes has shown potential as inhibitors of acetylcholinesterase, making them promising candidates for the development of new drugs against Alzheimer's disease.

JOURNAL OF MOLECULAR STRUCTURE (2022)

Article Chemistry, Multidisciplinary

Novel Coumarin-Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer's Disease

Elaheh Babaei et al.

Summary: In this research, a series of coumarin-based multifunctional anti-AD agents were synthesized and evaluated. Compound 3f showed the best activity, with potent inhibition of AChE and BuChE, as well as significant cell protective effects against H2O2-induced cell death and amyloid toxicity. It also exhibited greater potency in reducing beta-amyloid self and AChE-induced aggregation compared to the standard drug. These findings suggest that compound 3f holds promise as a multi-target-directed ligand against AD.

FRONTIERS IN CHEMISTRY (2022)

Article Biochemistry & Molecular Biology

In Silico and In Vitro Studies of Benzothiazole-Isothioureas Derivatives as a Multitarget Compound for Alzheimer's Disease

Martha Cecilia Rosales Hernandez et al.

Summary: Through docking simulations, 22 benzothiazole-isothiourea derivatives were evaluated for their inhibitory activity against AChE and A beta(1-42) aggregation, with compounds 3f, 3r, and 3t showing promising potential as multitarget agents for Alzheimer's disease treatment.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Neurosciences

Farnesyltransferase inhibitor LNK-754 attenuates axonal dystrophy and reduces amyloid pathology in mice

Leah K. Cuddy et al.

Summary: New data suggest that LNK-754 promoted axonal trafficking and function of endolysosomal compartments, reducing amyloid plaque deposition in 5XFAD mice. FTIs may have important therapeutic implications for treating AD.

MOLECULAR NEURODEGENERATION (2022)

Review Cell Biology

Tacrine Derivatives in Neurological Disorders: Focus on Molecular Mechanisms and Neurotherapeutic Potential

Saikat Mitra et al.

Summary: Tacrine, a drug used in the treatment of Alzheimer's disease, has certain mechanisms that influence neurotherapeutic activity. The diversity of analogues has piqued researchers' interest, and these analogues may have therapeutic potential in the treatment of neurological diseases.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2022)

Article Chemistry, Medicinal

The Chemotype of Chromanones as a Privileged Scaffold for Multineurotarget Anti-Alzheimer Agents

Tim Keuler et al.

Summary: The multifactorial nature of Alzheimer's disease necessitates the development of agents that can target multiple relevant pathways. In this study, we synthesized a series of tailored chromanones and evaluated their biological activities. One representative compound (compound 19) was identified, which exhibited balanced pharmacological properties and showed inhibitory activities against acetylcholinesterase, butyrylcholinesterase, monoamine oxidase-B, and high affinity to sigma 1 and sigma 2 receptors. Our findings provide a framework for the development of chromanone-based multineurotarget agents.

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE (2022)

Review Biochemistry & Molecular Biology

Recent advancements in chromone as a privileged scaffold towards the development of small molecules for neurodegenerative therapeutics

Hari Madhav et al.

Summary: This review highlights the recent advancements and developments of chromones as potential therapeutic molecules for neurodegenerative diseases. Different chromone derivatives have been studied as multi-target-directed ligands with potential inhibition against proteins and pathological processes associated with neurodegenerative diseases.

RSC MEDICINAL CHEMISTRY (2022)

Review Biochemistry & Molecular Biology

Repurposing Antihypertensive Drugs for the Management of Alzheimer's Disease

Christine Shing Wei Law et al.

Summary: This literature review discusses the potential of repurposing antihypertensives to treat Alzheimer's disease. The relationship between mid-life hypertension and AD has been established, leading to the hypothesis that antihypertensives could be beneficial in managing the disease. Four classes of antihypertensives, along with their potential limitations and prospects in serving as AD therapeutics, are explored in the review.

CURRENT MEDICINAL CHEMISTRY (2021)

Article Biochemistry & Molecular Biology

Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo [c]phenanthridine and berberine-based compounds on β-amyloid aggregation

Daniela Marasco et al.

Summary: Different isoquinoline alkaloids exhibit varying effects on beta-amyloid aggregation, with some compounds showing inhibitory effects and others showing promoting effects. Experimental results suggest that these compounds have the potential to serve as starting leads for the development of therapeutic strategies in neurodegenerative diseases.

CHEMICO-BIOLOGICAL INTERACTIONS (2021)

Review Clinical Neurology

The Development of Pharmacological Therapies for Alzheimer's Disease

Ping Lin et al.

Summary: Alzheimer's disease is a progressive neurodegenerative disorder without a cure. There is a growing need for more promising therapies due to the increasing elderly population worldwide. Recent efforts in clinical trials have focused on disease modification and symptomatic treatment, with varying results reported. The outcome of these trials and mechanisms of therapeutic agents are critical for guiding future drug development strategies.

NEUROLOGY AND THERAPY (2021)

Article Chemistry, Medicinal

Discovery of 7-aminophenanthridin-6-one as a new scaffold for matrix metalloproteinase inhibitors with multitarget neuroprotective activity

Damiano Rocchi et al.

Summary: Matrix metalloproteinases (MMPs) play a key role in neuroinflammatory events and brain damage associated with stroke. The study revealed a new compound with inhibitory effects on MMPs and potential neuroprotective activity against oxidative stress, providing a promising lead for future drug development. The compounds showed some selectivity for specific MMP enzymes and a noncompetitive inhibition mechanism was observed.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Clinical Neurology

The effects of JNJ-39393406 a positive allosteric nicotine modulator on mood and cognition in patients with unipolar depression: A double-blind, add-on, placebo-controlled trial

Michael Davidson et al.

Summary: Although positive allosteric modulators can delay receptor desensitization, the results of this study suggest that adding JNJ-39393406 did not significantly improve cognition and depressive symptoms in patients with unipolar depression.

EUROPEAN NEUROPSYCHOPHARMACOLOGY (2021)

Review Neurosciences

Flavonoids with Potential Anti-Amyloidogenic Effects as Therapeutic Drugs for Treating Alzheimer's Disease

Qixin Wang et al.

Summary: Alzheimer's disease is a common neurodegenerative disorder among the elderly, with a lack of effective treatments currently available to halt its progression. Most therapies only focus on symptom relief, highlighting an urgent need for disease-modifying therapies. Studies have shown that certain natural extracts and phytochemicals have a positive impact on brain aging, particularly flavonoids.

JOURNAL OF ALZHEIMERS DISEASE (2021)

Article Chemistry, Medicinal

Discovery of Umibecestat (CNP520): A Potent, Selective, and Efficacious β-Secretase (BACE1) Inhibitor for the Prevention of Alzheimer's Disease

Rainer Machauer et al.

Summary: Through optimization of BACE1 inhibitors, the study identified CNP520 (umibecestat), a compound with superior selectivity and pharmacokinetic properties that significantly reduced Aβ levels in mice and rats without any side effects, making it a potential candidate for Alzheimer's disease prevention in clinical studies.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Review Biochemistry & Molecular Biology

A comprehensive review on the biological interest of quinoline and its derivatives

Basavarajaiah Suliphuldevara Matada et al.

Summary: Quinoline and its derivatives are important compounds with diverse biological activities, making them significant for drug development. Many scientific communities have conducted research on these compounds and evaluated their biological activities and medicinal value.

BIOORGANIC & MEDICINAL CHEMISTRY (2021)

Review Biochemistry & Molecular Biology

Insights of 8-hydroxyquinolines: A novel target in medicinal chemistry

Rohini Gupta et al.

Summary: 8-Hydroxyquinoline is an important heterocyclic scaffold in organic and analytical chemistry, used for detecting metal ions and anions due to its chromophore properties. Recently, synthetic modification of 8-hydroxyquinoline has garnered attention for developing potent drug molecules for the treatment of diseases like cancer, HIV, and neurodegenerative disorders. The metal chelation properties of 8-hydroxyquinoline and its derivatives also make them potential drug candidates for various diseases.

BIOORGANIC CHEMISTRY (2021)

Article Neurosciences

Evaluation of Fluorinated Cromolyn Derivatives as Potential Therapeutics for Alzheimer's Disease

Timothy M. Shoup et al.

Summary: The study indicates that fluoro-cromolyn derivatives have low microglial cell toxicity and a positive impact on the uptake of Aβ(42), with derivative 4 showing enhanced phagocytosis/clearance of Aβ.

JOURNAL OF ALZHEIMERS DISEASE (2021)

Article Chemistry, Medicinal

Discovery of Atabecestat (JNJ-54861911): A Thiazine-Based β-Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor Advanced to the Phase 2b/3 EARLY Clinical Trial

Yuji Koriyama et al.

Summary: Atabecestat 1, a centrally efficacious BACE1 inhibitor, showed promising results in preclinical models but was discontinued in the EARLY trial due to significant elevation of liver enzymes, with subsequent analysis revealing dose-related cognitive worsening.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Cell Biology

Activation of Nurr1 with Amodiaquine Protected Neuron and Alleviated Neuroinflammation after Subarachnoid Hemorrhage in Rats

Huaijun Chen et al.

Summary: The pharmacological activation of Nurr1 with AQ alleviated neuron injury and neuroinflammation, potentially through the Nurr1/NF-kappa B/MMP9 pathway. AQ showed promise as a treatment strategy for subarachnoid hemorrhage by improving outcomes, reducing brain edema, and inhibiting proinflammatory cytokines.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2021)

Article Chemistry, Physical

Coumarin linked heterocyclic hybrids: A promising approach to develop multi target drugs for Alzheimer's disease

Asif Husain et al.

Summary: Alzheimer's disease is a major progressive cortical degenerative disease of the brain in the elderly, causing significant socioeconomic burden. A hybridized approach using multi-target directed ligands for developing therapeutic agents for AD has gained attention, with 20% of recent drug approvals following this strategy. The strategy of coupling coumarin scaffold with other bioactive pharmacophores has been highlighted as important for developing AD therapy.

JOURNAL OF MOLECULAR STRUCTURE (2021)

Article Biochemistry & Molecular Biology

Neuroprotective Action of Multitarget 7-Aminophenanthridin-6(5H)-one Derivatives against Metal-Induced Cell Death and Oxidative Stress in SN56 Cells

Paula Moyano et al.

Summary: Neurodegenerative diseases are linked to brain metal accumulation, oxidative stress, and neuronal cell death. Some compounds have been found to inhibit metal-induced cell death and oxidative stress, exhibit selective chelating activity, and provide neuroprotective effects through induction of the Nrf2 pathway and overexpression of antioxidant enzymes.

ACS CHEMICAL NEUROSCIENCE (2021)

Article Clinical Neurology

Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease

Dawn C. Matthews et al.

Summary: This study evaluated the potential efficacy and safety of riluzole in patients with Alzheimer's disease compared to placebo using neuroimaging biomarkers, showing that riluzole-treated participants had better preserved cerebral glucose metabolism compared to placebo group, with positive correlation between cognitive performance and regional cerebral glucose metabolism, as well as potential engagement of the glutamatergic system by riluzole in the posterior cingulate. These findings support further powered, longer duration studies of riluzole as a potential intervention for Alzheimer's disease.

BRAIN (2021)

Article Chemistry, Medicinal

Novel pyridine-containing sultones: Structure-activity relationship and biological evaluation as selective AChE inhibitors for the treatment of Alzheimer's disease

Hong Zhang et al.

Summary: Novel pyridine-containing sultones were synthesized and evaluated for their cholinesterase inhibitory activity, showing selective AChE inhibition. Compound B4 was identified as a selective AChE inhibitor with good fitting into TcAChE via hydrogen interactions. Studies also confirmed B4's cognitive performance improvement in scopolamine-treated mice, indicating potential benefits for treating Alzheimer's disease through AChE inhibition.

CHEMMEDCHEM (2021)

Review Biochemistry & Molecular Biology

Recent Progress on Biological Activity of Amaryllidaceae and Further Isoquinoline Alkaloids in Connection with Alzheimer's Disease

Lucie Cahlikova et al.

Summary: Alzheimer's disease is a progressive age-related neurodegenerative disease, with the exact pathogenesis still remaining unclear and treatment currently limited to symptomatic relief. With increasing life expectancy worldwide, the rates of AD are predicted to rise significantly, highlighting an urgent need for new treatment drugs. Alkaloids, especially Amaryllidaceae alkaloids and isoquinoline alkaloids, show promise as potential candidates for AD treatment.

MOLECULES (2021)

Article Multidisciplinary Sciences

Quinacrine directly dissociates amyloid plaques in the brain of 5XFAD transgenic mouse model of Alzheimer's disease

Sohui Park et al.

Summary: Alzheimer's disease is characterized by abnormal accumulation of amyloid-beta in the brain, leading to neuroinflammation and synaptic dysfunction. Quinacrine has been found to dissociate A beta plaques, reduce plaque formation, and improve synaptic function in transgenic mice.

SCIENTIFIC REPORTS (2021)

Review Biochemistry & Molecular Biology

Oxidative Stress and Beta Amyloid in Alzheimer's Disease. Which Comes First: The Chicken or the Egg?

Elena Tamagno et al.

Summary: The pathogenesis of Alzheimer's disease involves the accumulation of beta amyloid and vulnerability of the brain to oxidative stress, which are linked to each other. It is difficult to determine which comes first, Aβ or oxidative stress. Evidence suggests that oxidative stress occurs early in the development of Alzheimer's disease and plays a crucial role in the manifestation of clinical and pathological symptoms.

ANTIOXIDANTS (2021)

Review Clinical Neurology

Multi-Target Directed Ligands (MTDLs): Promising Coumarin Hybrids for Alzheimer's Disease

Rohit Bhatia et al.

Summary: Alzheimer's disease is an age-associated neurodegenerative disorder characterized by memory loss and cognitive decline. The exact pathogenesis of the disease is still unknown, with mechanisms such as decreased acetylcholine concentration and amyloid deposition believed to be involved. Current drugs against Alzheimer's provide only symptomatic relief, prompting the investigation of molecular hybrids as potential multi-target therapies. Coumarin hybrids show promise in targeting multiple pathways associated with Alzheimer's, but further research is needed to fully understand their therapeutic potential.

CURRENT ALZHEIMER RESEARCH (2021)

Article Clinical Neurology

Amyloid and APOE Status of Screened Subjects in the Elenbecestat MissionAD Phase 3 Program

Claire Roberts et al.

Summary: The study found differences in characteristics of APOE epsilon 4 and amyloid positive subjects in the early AD screening cohort, with variation in positivity rates by country and geographical region.

JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE (2021)

Review Neurosciences

Nimodipine Reappraised: An Old Drug with a Future

Andrew P. Carlson et al.

CURRENT NEUROPHARMACOLOGY (2020)

Review Chemistry, Medicinal

Propargylamine-derived multi-target directed ligands for Alzheimer's disease therapy

Maria do Carmo Carreiras et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2020)

Review Biochemistry & Molecular Biology

Intracellular Calcium Dysregulation by the Alzheimer's Disease-Linked Protein Presenilin 2

Luisa Galla et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Article Neurosciences

G-Protein Coupled Receptors and Tau-different Roles in Alzheimer's Disease

Hariharakrishnan Chidambaram et al.

NEUROSCIENCE (2020)

Review Chemistry, Inorganic & Nuclear

Metal complexes that bind to the amyloid-β peptide of relevance to Alzheimer's disease

Luiza M. F. Gomes et al.

COORDINATION CHEMISTRY REVIEWS (2020)

Review Biotechnology & Applied Microbiology

Multitarget Therapeutic Strategies for Alzheimer's Disease: Review on Emerging Target Combinations

Samuele Maramai et al.

BIOMED RESEARCH INTERNATIONAL (2020)

Review Clinical Neurology

Drug repositioning and repurposing for Alzheimer disease

Clive Ballard et al.

NATURE REVIEWS NEUROLOGY (2020)

Review Biochemistry & Molecular Biology

The Role of Mitochondrial Calcium Homeostasis in Alzheimer's and Related Diseases

Kerry C. Ryan et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Review Cell Biology

Clinical trials of new drugs for Alzheimer disease

Li-Kai Huang et al.

JOURNAL OF BIOMEDICAL SCIENCE (2020)

Review Biochemistry & Molecular Biology

Anti-cholinesterase hybrids as multi-target-directed ligands against Alzheimer's disease (1998-2018)

Pankaj Mishra et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2019)

Article Medicine, General & Internal

Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease

Michael F. Egan et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Review Pharmacology & Pharmacy

Drug repurposing: a promising tool to accelerate the drug discovery process

Vineela Parvathaneni et al.

DRUG DISCOVERY TODAY (2019)

Review Pharmacology & Pharmacy

Developments with multi-target drugs for Alzheimer's disease: an overview of the current discovery approaches

Juan F. Gonzalez et al.

EXPERT OPINION ON DRUG DISCOVERY (2019)

Review Biochemistry & Molecular Biology

The Nervous System Relevance of the Calcium Sensing Receptor in Health and Disease

Maria Lo Giudice et al.

MOLECULES (2019)

Article Neurosciences

Role of GPCR signaling and calcium dysregulation in Alzheimer's disease

Sushma et al.

MOLECULAR AND CELLULAR NEUROSCIENCE (2019)

Article Neurosciences

In Silico Studies in Drug Research Against Neurodegenerative Diseases

Farahnaz Rezaei Makhouri et al.

CURRENT NEUROPHARMACOLOGY (2018)

Article Medicine, General & Internal

Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease

Michael F. Egan et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Review Biochemistry & Molecular Biology

Medicinal chemistry of acridine and its analogues

Parteek Prasher et al.

MEDCHEMCOMM (2018)

Article Medicine, General & Internal

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial

Brian Lawlor et al.

PLOS MEDICINE (2018)

Review Chemistry, Medicinal

Oxidative Stress and Neurodegenerative Diseases: Looking for a Therapeutic Solution Inspired on Benzopyran Chemistry

Alexandra Gaspar et al.

CURRENT TOPICS IN MEDICINAL CHEMISTRY (2015)

Article Food Science & Technology

Reactivity of phenolic compounds towards free radicals under in vitro conditions

Sindhu Mathew et al.

JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE (2015)

Review Medicine, General & Internal

Latrepirdine for Alzheimer's disease

Sarah Chau et al.

COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2015)

Article Biochemistry & Molecular Biology

Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

J. W. Steele et al.

MOLECULAR PSYCHIATRY (2013)

Article Developmental Biology

Matrix metalloproteinase (MMP)-2 and MMP-9 activities in human seminal plasma

K Shimokawa et al.

MOLECULAR HUMAN REPRODUCTION (2002)